The Role of Mitochondrial Respiration in the Cardioprotective Capacity of IPC in Diabetic and Non-diabetic Patients

Overview

The overall aim of this study is to examine the role of mitochondrial respiration in human diabetic tissue before and after ischemia. Furthermore we will examine the ability of ischemic preconditioning (IPC) to preserve the mitochondrial function and hemodynamic performance of both non-diabetic and diabetic fibers after ischemia. To increase our understanding on the metabolic changes during ischemia in both non-diabetic and diabetic tissue we will use Dimethyl Malonate and examine the impact of this blockade on post-ischemic mitochondrial respiration.

20 diabetic and 20 non-diabetic patients undergoing elective CABG surgery or other heart surgery where extracorporal circulation is used will be included in the study. The patiens will not be given any treatment prior to the operation. During the cardiac surgery a small sample of the heart is routinely removed when the patient is connection to the heart-lung machine. From this tissue sample it is possible to isolate muscle trabeculae which will be used in an atrial strip model and randomized to one of four types of treatment. Simultaneously with the isolation of the trabeculae, a fifth trabecular will be used to assess mitochondrial respiration at baseline. Group 1 will serve as a sham control, group 2 will serve as ischemic control and receive an extended period of hypoxia, Group 3 will be treated with ischemic preconditioning, where short periods of non lethal lack of oxygen will be given directly to the tissue (after removal from the patient) prior to the extended period of hypoxia, Group 4 will receive dimethyl malonate prior to the prolonged hypoxia.